Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer

Soichiro Ako, Hironari Kato, Kazuhiro Nouso, Hideaki Kinugasa, Hiroyuki Terasawa, Hiroshi Matushita, Saimon Takada, Yosuke Saragai, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Daisuke Nobuoka, Ryuichi Yoshida, Yuzo Umeda, Takahito Yagi, Hiroyuki Okada

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called “liquid biopsy”) is recently developed. Aims: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. Methods: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. Results: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36–9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). Conclusions: In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.

Original languageEnglish
JournalCancer Biology and Therapy
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Chemotherapy
  • disease-free survival
  • droplet digital polymerase chain reaction
  • progression-fee survival
  • surgical resection

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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